We have reported that the two pairs of histone acetyltransferases (HATs), GCN5/PCAF and CBP/p300, are specifically required for H3K9 acetylation (H3K9ac) and H3K18/27 acetylation (H3K18/27ac), respectively, in cells. Further, we show that CBP/p300 and their HAT activities are essential, while GCN5/PCAF and associated H3K9ac are dispensable, for ligand-induced nuclear receptor target gene expression. These results highlight the substrate and site specificities of HATs in cells, demonstrate the distinct roles of GCN5/PCAF- and CBP/p300-mediated histone acetylations in gene activation, and suggest an important role of CBP/p300-mediated H3K18/27ac in nuclear receptor target gene expression (Jin Q. et al., EMBO J, 2011). Viral infection triggers innate immune signaling, which in turn induces interferon- (IFN-) production to establish innate antiviral immunity. Previous studies showed that Gcn5 (Kat2a), a histone acetyltransferase (HAT) with partial functional redundancy with PCAF (Kat2b), and Gcn5/PCAF-mediated histone H3K9 acetylation (H3K9ac) are enriched on the active IFNB gene promoter. However, whether Gcn5/PCAF and H3K9ac regulate IFN- production is unknown. In a recent study, we show that Gcn5/PCAF-mediated H3K9ac correlates well with, but is surprisingly dispensable for, the expression of endogenous IFNB and the vast majority of active genes in fibroblasts. Instead, Gcn5/PCAF repress IFN- production and innate antiviral immunity in several cell types in a HAT-independent and non-transcriptional manner: by inhibiting the innate immune signaling kinase TBK1 in the cytoplasm. Our results thus identify Gcn5 and PCAF as negative regulators of IFN- production and innate immune signaling (Jin Q. et al., EMBO Rep, 2014). Using GR as the model system to understand epigenomic regulation of nuclear receptor target gene activation, we have found that GR activates expression of early adipogenic genes by recruiting H3K27 acetyltransferase CBP/p300 to promote activation of C/EBP-primed enhancers. In addition, using conditional knockout mice and derived preadipocytes, we show that surprisingly, endogenous GR and two early adipogenic TFs, Krox20 and KLF4, are largely dispensable for adipogenesis in culture and adipose tissue development in mice. In contrast, the master adipogenic transcription factor PPARgamma is essential. These results challenge the existing model on transcriptional regulation in the early phase of adipogenesis and highlight the need of studying adipogenesis in vivo.

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Park, Young-Kwon; Wang, Limin; Giampietro, Anne et al. (2017) Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor ? in Adipogenesis. Mol Cell Biol 37:
Park, Young-Kwon; Ge, Kai (2017) Glucocorticoid Receptor Accelerates, but Is Dispensable for, Adipogenesis. Mol Cell Biol 37:
Jang, Younghoon; Wang, Chaochen; Zhuang, Lenan et al. (2017) H3K4 Methyltransferase Activity Is Required for MLL4 Protein Stability. J Mol Biol 429:2046-2054
Jin, Qihuang; Wang, Chaochen; Kuang, Xianghong et al. (2014) Gcn5 and PCAF regulate PPAR? and Prdm16 expression to facilitate brown adipogenesis. Mol Cell Biol 34:3746-53
Kumar, Amit; Lualdi, Margaret; Loncarek, Jadranka et al. (2014) Loss of function of mouse Pax-Interacting Protein 1-associated glutamate rich protein 1a (Pagr1a) leads to reduced Bmp2 expression and defects in chorion and amnion development. Dev Dyn 243:937-47
Xu, Shiliyang; Grullon, Sean; Ge, Kai et al. (2014) Spatial clustering for identification of ChIP-enriched regions (SICER) to map regions of histone methylation patterns in embryonic stem cells. Methods Mol Biol 1150:97-111
Lee, Ji-Eun; Ge, Kai (2014) Transcriptional and epigenetic regulation of PPAR? expression during adipogenesis. Cell Biosci 4:29
Jin, Qihuang; Zhuang, Lenan; Lai, Binbin et al. (2014) Gcn5 and PCAF negatively regulate interferon-? production through HAT-independent inhibition of TBK1. EMBO Rep 15:1192-201
Lee, Ji-Eun; Wang, Chaochen; Xu, Shiliyang et al. (2013) H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation. Elife 2:e01503
Park, Jun Hong; Kang, Hong Jun; Kang, Soo Im et al. (2013) A multifunctional protein, EWS, is essential for early brown fat lineage determination. Dev Cell 26:393-404

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